Anti-Müllerian hormone, testosterone, and insulin-like peptide 3 as biomarkers of Sertoli and Leydig cell function during deslorelin-induced testicular downregulation in the dog.

The role of anti-Müllerian hormone (AMH) and insulin-like peptide 3 (INSL3) in male infertility is not fully understood. We used the downregulated testis as a model of gonadotropin-dependent infertility. Serum testosterone and AMH concentrations were studied in five adult male Beagles implanted (day 0) with 4.7 mg deslorelin (Suprelorin®, Virbac) (DES group). Testicular expression of LH receptor (LHR) and androgen receptor (AR), AMH, type 2 AMH receptor (AMHR2), INSL3 and its receptor (RXFP2) was evaluated 112 days (16 weeks) after deslorelin treatment by qPCR and immunohistochemistry, and compared to untreated adult (CON, n = 6) and prepubertal (PRE, n = 8) dogs. Serum testosterone concentration decreased significantly by the onset of aspermia on study day 14 (four dogs) or day 21 (one dog), and was baseline on day 105 (week 15). In contrast, serum AMH started to increase only after the onset of aspermia and reached the maximum detectable concentration of the assay by day 49-105 in individual dogs. Testicular LHR gene expression in DES was lower than in CON and PRE (P < 0.0001), while AR gene expression in DES was similar to CON and significantly higher than PRE (P < 0.0001). Testicular AMH expression in DES was intermediate compared to the lowest mRNA levels found in CON and the highest in PRE (P ≤ 0.006). AMHR2 gene expression was similar between groups. AMH protein was detected in Sertoli cells only, while AMHR2 immunoreactivity was principally detected in Leydig cells which appeared to be increased in DES. INSL3 and RXFP2 gene expression was significantly downregulated in the DES testis along with noticeably weak Leydig cell immunosignals compared to CON. In conclusion, deslorelin treatment caused testicular LH insensitivity without affecting androgen sensitivity, and de-differentiation of Sertoli and Leydig cells. In DES, upregulation of the AMH-AMHR2 feed-back loop and downregulation of the INSL3-RXFP2 feed-forward loop are paracrine-autocrine mechanisms that may additionally regulate testosterone production independent of gonadotropins. Our results support AMH and INSL3 as unique biomarkers and paracrine-autocrine regulators of testis function involved in the intimate interplay between Sertoli and Leydig cells.

Constructing Well-Being and Poverty Dimensions on Political Grounds.

The paper addresses the problem of justifying ethically sound dimensions of poverty or well-being for use in a multidimensional framework. We combine Sen's capability approach and Rawls' method of political constructivism and argue that the constitution and its interpretative practice can serve as an ethically suitable informational basis for selecting dimensions, under certain conditions. We illustrate our Constitutional Approach by deriving a set of well-being dimensions from an analysis of the Italian Constitution. We argue that this method is both an improvement on those used in the existing literature from the ethical point of view, and has a strong potential for providing the ethical basis of a conception of well-being for the public affairs of a pluralist society. In the final part, we elaborate on the implications for measuring well-being based on data, by ranking Italian regions in terms of well-being, and pointing out the differences in results produced by different methods.

What is wrong with the emergency justification of compulsory medical service?

Michael Blake holds that liberal states are precluded from introducing compulsory medical service to improve access to health care under conditions of critical health worker shortage. "Emergency circumstances" are the only exception when the suspension of liberty may be justified. I argue that there are three problems with Blake's emergency justification of compulsory service. First, his concept of emergency is vague. Second, his account does not really rely on emergency as much as liberty. Third, his conception of permissible restrictions of liberty is too narrow. I argue that liberties may be limited to some degree, temporarily, for the sake of attaining the capacities necessary for the exercise of liberties and for safeguarding the social conditions of the right to health. I conclude that in poor societies, temporarily delaying emigration through a highly qualified compulsory medical service can sometimes be justified.

Thyroxin and progesterone concentrations in pregnant, nonpregnant bitches, and bitches during abortion.

Serum progesterone and thyroxin concentrations were measured weekly until 61 to 62 days after ovulation in 24 pregnant bitches and in the control group of nine nonpregnant bitches in the luteal phase. Fourteen of the 24 dogs had a normal pregnancy and parturition. Ten of the 24 dogs showed mucinous or colored vaginal discharge, decreased appetite, or lethargy. These initial signs of abortion or fetal resorption were noted during the fourth week of pregnancy, and the process occurred over the next 2 weeks. Progesterone and thyroxin concentrations were measured by quantitative ELISAs validated to dog serum. The serum progesterone concentrations of the group going through abortions differed significantly from the third week until the end of the eighth week. The mean serum thyroxin concentrations of healthy pregnant and nonpregnant groups significantly exceeded the reference range (20-45 nmol/L). The serum thyroxin concentrations in the abortion group were between 16.15 ± 3.17 and 40.78 ± 8.97 nmol/L. The values in this group were significantly different from the other two groups at the third week of the luteal phase. Clinical signs of abortion or fetus resorption manifested in midpregnancy. The clinical signs of abortion coincided in each case with a low serum progesterone concentration (<10 ng/mL). This phenomenon indicated, in contrast with other studies, that the decrease of serum progesterone below 10 ng/mL at the fourth week of pregnancy may signal impending abortion. In the second half of pregnancy, the thyroid gland was not able to respond adequately to the elevated requirement in thyroid hormone, although in other periods of the ovarian cycle, there were no clinical signs of hypothyroidism.

Humanity and Justice in Global Health: Problems with Venkatapuram's Justification of the Global Health Duty.

One of the most ambitious and sophisticated recent approaches to provide a theory of global health justice is Sridhar Venkatapuram's recent work. In this commentary, we first outline the core idea of Venkatapuram's approach to global health justice. We then argue that one of the most important elements of the account, Venkatapuram's basis of global health duties, is either too weak or assumed implicitly without a robust justification. The more explicit grounding of the duty to protect and promote health capabilities is based on Martha Nussbaum's version of the capability approach. We argue that this foundation gives rise to humanitarian duties rather than duties of justice proper. Venkatapuram's second argument from the social determinants of health thesis is instead a stronger candidate for grounding duties of justice. However, as a justificatory argument, it is only alluded to and has not yet been spelled out sufficiently. We offer plausible justificatory steps to fill this gap and draw some implications for global health action. We believe this both strengthens Venkatapuram's approach and serves to broaden the basis for future action in the area of global health.

Body fat distribution and metabolic consequences - Examination opportunities in dogs.

The relationship between metabolic disorders and the distribution of fat in different body regions is not clearly understood in humans. The aim of this study was to develop a suitable method for assessing the regional distribution of fat deposits and their metabolic effects in dogs. Twenty-five dogs were subjected to computed tomographic (CT) imaging and blood sampling in order to characterise their metabolic status. The different fat areas were measured on a cross-sectional scan, and the animals' metabolic status was evaluated by measuring fasting glucose, insulin and leptin levels. The volume of visceral adipose tissue is the main determinant of leptin levels. The correlation of visceral fat volume and leptin concentration was found to be independent of insulin levels or the degree of insulin resistance. There was a positive correlation between the visceral to subcutaneous fat volume ratio and serum insulin concentration, and a similar trend was observed in the relationship of fat ratio and insulin resistance. The distribution of body fat essentially influences the metabolic parameters in dogs, but the effects of adiposity differ between humans and dogs. The findings can facilitate a possible extrapolation of results from animal studies to humans with regard to the metabolic consequences of different obesity types.

Ethics and policy of medical brain drain: a review.

Health-worker migration, commonly called "medical brain drain", refers to the mass migration of trained and skilled health professionals (doctors, nurses, midwives) from low-income to high-income countries. This is currently leaving a significant number of poor countries, particularly in sub-Saharan Africa, with critical staff shortages in the healthcare sector. A broad consensus exists that, where medical brain drain exacerbates such shortages, it is unethical, and this review presents the main arguments underpinning this view. Notwithstanding the general agreement, which policies are justifiable on ethical grounds to tackle brain drain and how best to go about implementing them remains controversial. The review offers a discussion of the specific ethical issues that have to be taken into account when deciding which policy measures to prioritise and suggests a strategy of policy implementation to address medical brain drain as a matter of urgency.